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| http://purl.uniprot.org/citations/23165767 | http://www.w3.org/2000/01/rdf-schema#comment | "The chloride channel CLC-3 is expressed in the brain on synaptic vesicles and postsynaptic membranes. Although CLC-3 is broadly expressed throughout the brain, the CLC-3 knockout mouse shows complete, selective postnatal neurodegeneration of the hippocampus, suggesting a crucial role for the channel in maintaining normal brain function. CLC-3 channels are functionally linked to NMDA receptors in the hippocampus; NMDA receptor-dependent Ca(2+) entry, activation of Ca(2+)/calmodulin kinase II and subsequent gating of CLC-3 link the channels via a Ca(2+)-mediated feedback loop. We demonstrate that loss of CLC-3 at mature synapses increases long-term potentiation from 135 ± 4% in the wild-type slice preparation to 154 ± 7% above baseline (P < 0.001) in the knockout; therefore, the contribution of CLC-3 is to reduce synaptic potentiation by ∼40%. Using a decoy peptide representing the Ca(2+)/calmodulin kinase II phosphorylation site on CLC-3, we show that phosphorylation of CLC-3 is required for its regulatory function in long-term potentiation. CLC-3 is also expressed on synaptic vesicles; however, our data suggest functionally separable pre- and postsynaptic roles. Thus, CLC-3 confers Cl(-) sensitivity to excitatory synapses, controls the magnitude of long-term potentiation and may provide a protective limit on Ca(2+) influx."xsd:string |
| http://purl.uniprot.org/citations/23165767 | http://purl.org/dc/terms/identifier | "doi:10.1113/jphysiol.2012.243485"xsd:string |
| http://purl.uniprot.org/citations/23165767 | http://purl.uniprot.org/core/author | "Nelson D.J."xsd:string |
| http://purl.uniprot.org/citations/23165767 | http://purl.uniprot.org/core/author | "Farmer L.M."xsd:string |
| http://purl.uniprot.org/citations/23165767 | http://purl.uniprot.org/core/author | "Le B.N."xsd:string |
| http://purl.uniprot.org/citations/23165767 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23165767 | http://purl.uniprot.org/core/name | "J Physiol"xsd:string |
| http://purl.uniprot.org/citations/23165767 | http://purl.uniprot.org/core/pages | "1001-1015"xsd:string |
| http://purl.uniprot.org/citations/23165767 | http://purl.uniprot.org/core/title | "CLC-3 chloride channels moderate long-term potentiation at Schaffer collateral-CA1 synapses."xsd:string |
| http://purl.uniprot.org/citations/23165767 | http://purl.uniprot.org/core/volume | "591"xsd:string |
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